TY  - JOUR
AU  - Wang, Changwen
AU  - Stöffler, Nadja
AU  - Liu, Haikun
TI  - Laboratory-Engineered Glioblastoma Organoid Culture and Drug Screening.
JO  - JoVE journal
VL  - 215
SN  - 1940-087X
CY  - Cambridge, MA
PB  - JoVE
M1  - DKFZ-2025-00245
SP  - e67593
PY  - 2025
N1  - #EA:A240#LA:A240#
AB  - Glioblastoma (GBM) is described as a group of highly malignant primary brain tumors and stands as one of the most lethal malignancies. The genetic and cellular characteristics of GBM have been a focal point of ongoing research, revealing that it is a group of heterogeneous diseases with variations in RNA expression, DNA methylation, or cellular composition. Despite the wealth of molecular data available, the lack of transferable pre-clinic models has limited the application of this information to disease classification rather than treatment stratification. Transferring the patients' genetic information into clinical benefits and bridging the gap between detailed descriptions of GBM, genotype-phenotype associations, and treatment advancements remain significant challenges. In this context, we present an advanced human GBM organoid model, the Laboratory Engineered Glioblastoma Organoid (LEGO), and illustrate its use in studying the genotype-phenotype dependencies and screening potential drugs for GBM. Utilizing this model, we have identified lipid metabolism dysregulation as a critical milestone in GBM progression and discovered that the microsomal triglyceride transfer protein inhibitor Lomitapide shows promise as a potential treatment for GBM.
KW  - Glioblastoma: genetics
KW  - Glioblastoma: pathology
KW  - Humans
KW  - Organoids: metabolism
KW  - Organoids: drug effects
KW  - Brain Neoplasms: genetics
KW  - Brain Neoplasms: pathology
KW  - Drug Screening Assays, Antitumor: methods
KW  - Drug Evaluation, Preclinical: methods
LB  - PUB:(DE-HGF)16
C6  - pmid:39868688
DO  - DOI:10.3791/67593
UR  - https://inrepo02.dkfz.de/record/298341
ER  -